Novel NEXMIF pathogenic variant in a boy with severe autistic features, intellectual disability, and epilepsy, and his mildly affected mother

Article Article scientifique Article Novel NEXMIF pathogenic variant in a boy with severe autistic features, intellectual disability, and epilepsy, and his mildly affected mother eng 2018 author Lambert Nelle 847492 author Dauve Corinne 847148 author Ranza Emmanuelle Nathalie 517664 author Makrythanasis Periklis 638085 author Santoni Federico 681638 author Sloan Bena Frédérique 629243 author Gimelli Stefania 663673 author Blouin Jean-Louis 513663 author Guipponi Michel 118157 author Bottani Armand 513397 author Antonarakis Stylianos 22813 author Kosel Markus Mathaus 668114 author Fluss Joel Victor 28801 author Giacobino Ariane 28204 847-850 10.1038/s10038-018-0459-2 29717186 1434-5161 Intellectual disability (ID) and autism spectrum disorders are complex neurodevelopmental disorders occurring among all ethnic and socioeconomic groups. Pathogenic variants in the neurite extension and migration factor (NEXMIF) gene (formerly named KIAA2022) on the X chromosome are responsible for ID, autistic behavior, epilepsy, or dysmorphic features in males. Most affected females described had a milder phenotype or were asymptomatic obligate carriers. We report here for the first time mother-to-son transmission of a novel NEXMIF truncating variant without X-inactivation skewing in the blood. Truncating gene variant leads to symptomatic mother to severely affected son transmission. Our findings emphasize that NEXMIF sequencing should be strongly considered in patients with unexplained autism spectrum disorder, ID, and epilepsy, irrespective of gender. Such testing could increase our knowledge of the pathogenicity of NEXMIF variants and improve genetic counseling. Adult Autism Spectrum Disorder/diagnosis/genetics/physiopathology Base Sequence Child Epilepsy/diagnosis/genetics/physiopathology Female Gene Expression Hemizygote Heterozygote Humans Intellectual Disability/diagnosis/genetics/physiopathology Male Maternal Inheritance Nerve Tissue Proteins/genetics Pedigree Sequence Deletion Severity of Illness Index X Chromosome Inactivation Dewey 576.5 Dewey 616.89 Dewey 618 Swiss National Science Foundation NCCR SYNAPSY: The synaptic bases of mental diseases (phase I) 125759 CH 135 Département de médecine génétique et développement 21D 58 Département de pédiatrie, gynécologie et obstétrique 223 60 Département de psychiatrie 225 false 580 Groupe Giacobino Ariane (génétique) 923 573 Troubles du développement intellectuel et du spectre de l'autisme chez l'adulte 916 Journal of Human Genetics 63 7 9fd7a94e-c191-4eba-9afd-619f95970af9 Article (Published version) Restricted s10038-018-0459-2.pdf 613962 application/pdf b7f4c28d-34be-4f82-a770-fa9ab08ffe84 Article (Accepted version) Public JHG-18-017R1.pdf 276116 application/pdf Restricted 2020-03-30 openAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique Faculté de médecine / Section de médecine clinique / Département de psychiatrie

Title	Published in	Year	Views	Downloads

Novel NEXMIF pathogenic variant in a boy with severe autistic features, intellectual disability, and epilepsy, and his mildly affected mother	Journal of Human Genetics	2018	464	557
Le handicap intellectuel chez l'adulte : concepts actuels et défis dans l'approche clinique	Revue médicale suisse	2017	640	5

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Dauve, Corinne